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Brains & Minds II: Every Brain Is Different

Earlier this week I was the token non-scientist on a panel to discuss the future of biomedicine at the Biotechnology Industry Association's huge annual convention. (Our discussion is described semi-accurately here.) The big trend I see is the convergence of genomic information, frequent real-time monitoring of metabolic function (I got a laugh by talking about "smart toilets"), personalized pharmacology, and patient activism.

In the Manhattan Institute's online newsletter Medical Progress Today John A. Fossella writes about personalized medicine as it could affect mental health treatments. Here's an excerpt:

More recently, genomic analyses have been synthesized with brain imaging studies so that physicians and researchers might understand how genetic biomarkers that predispose individuals to mental illness can affect brain structure and function. For example, the gene for the serotonin transporter (5HTT) has for many years been shown to contribute to risk for anxiety disorders. The protein encoded by the 5HTT gene is the target of a class of effective antidepressant compounds known as selective serotonin reuptake inhibitors (SSRIs).

In 2002, the first link between variation in the 5HTT gene and brain activity was found to occur in a brain region known as the amygdala, where emotional memories are stored and relayed. Individuals who carry a type of 5HTT genetic predisposition for anxiety were found to have a more active amygdala when viewing stimuli designed to illicit [sic--vp] emotional responses. Thus, a complete synthesis between brain activity, genetic variation and pharmacotherapy has been accomplished, and it is now possible to view the effects of drug treatment through brain imaging. The implications are far reaching, but at face level, serve to match a certain biological process to more effective treatment options.

In order to better realize the promise of this basic research, the NIH Roadmap has recognized and mandated the need for translating these fundamental and highly technical findings into layman's tools that facilitate the everyday relationship between physician and patient. For instance, successful medication selection is one of the most long-standing challenges in psychiatry. Patients taking antipsychotic medication often experience side effects such as tardive dyskinesia, weight gain and diabetes.

Some of these side effects can now be addressed with genetic information; patients with certain variants of the CYP2D6 gene metabolize medications more poorly and thus experience greater risk of side effects. The FDA-approved AmpliChip® provides a clinical platform for screening of this and other metabolic genes. A number of other studies point to the dopamine D3 receptor gene as a mediator of tardive dyskinesia, while other studies have identified specific genetic variants that influence the magnitude of obesity-related side effects.